Synovial Gene Signatures Associated with the Development of Rheumatoid Arthritis in At Risk Individuals
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Tineke de Jong
PROVIDER: E-MTAB-11874 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Synovial biopsies from rheumatoid arthritis patients were obtained and profiled using RNA-seq. Patients were stratified according to the number of swollen joints they had (SJC, swollen joint count) and divided in three groups for the differential expression analysis: None (SJC = 0), Low (1<= SJC <= 8), High (SJC > 8).
2021-04-26 | E-MTAB-6684 | biostudies-arrayexpress
Project description:Synovial biopsies from rheumatoid arthritis patients were obtained and profiled using bisulfite-seq for whole-genome DNA methylation. Patients were stratified according to the number of swollen joints they had (SJC, swollen joint count) and divided in three groups for the differential expression analysis: None (SJC = 0), Low (1<= SJC <= 8), High (SJC > 8).
2021-04-26 | E-MTAB-6638 | biostudies-arrayexpress
Project description:Inflammatory tissues are characterized by low oxigen concentrations (hypoxia). These conditions are very different from that usually present in tissue cultures where transcriptomic profiles of human fibroblasts from inflammatory tissues have been previously analysed. The aim of this study was to characterize the changes on gene expression induced by hypoxia in human synovial fibroblasts. We used microarray expression profiling in paired normoxic and hypoxic cultures of healthy and rheumatoid arthritis (RA) synovial fibroblasts (HSF and RASF). Hypoxia induces significant changes on the expression of large groups of genes in both HSF and RASF. The hypoxic and normoxic profiles are also different between both groups. These data demonstrate that hypoxia induces significant changes on gene expression in HSF and RASF and identify differences between RASF and HSF. Synovial fibroblasts obtained from 6 patients with rheumatoid arthritis (RASF) and 6 sex and age matched adult healthy donors (HSF) were used. SF cultures were incubated for 22 hours under normoxic or hypoxic (0.5% O2) conditions. Nine experiments per group were performed, single experiments with three SF lines, and duplicated in other three lines per group. All 18 normoxia-hypoxia experiments (36 microarray data) were used for paired analysis of the changes induced by hypoxia in HSF or RASF.
2010-12-10 | E-GEOD-21959 | biostudies-arrayexpress
Project description:mRNA expression levels in synovial fibroblasts in 6 rheumatoid arthritis patients versus 6 osteoarthritis patients. Experiment Overall Design: Synovial tissue was obtained from open joint replacement surgery or Experiment Overall Design: arthroscopic synovectomy. Patients with RA or OA (n = 6 each for gene expression analysis and further patients for validation experiments) were classified according to the ACR criteria.
2009-04-28 | E-GEOD-7669 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE18023: Mice with FIA develop anti-native and anti-in vitro citrullinated fibrinogen antibodies GSE18024: FIA plasma induces arthritis in naïve mice GSE18025: Fibrinogen-reactive T cells transfer disease to naïve mice Refer to individual Series
2010-05-05 | E-GEOD-18073 | biostudies-arrayexpress
Project description:Anti-citrullinated protein antibodies (ACPAs) are one of the hallmarks in rheumatoid arthritis (RA), but the in vivo function remained unclear. To investigate the effects of ACPAs, we expressed monoclonal ACPAs derived from RA patients, and analyzed the functions in mouse models, as well as the reactivity to tissue and peptides/proteins. All ACPAs showed no arthritogenicity and could not induce pain-like behavior in mice whereas one of them (E4) profoundly protected against antibody-induced arthritis. E4 showed a tissue binding pattern restricted to skin epithelial cells, to macrophages and dendritic cells in lymphoid tissue and to cartilage from mouse and human arthritic joints. Proteomic analysis showed that E4 had a distinct binding pattern to macrophage and RA synovial fluid proteins (e.g. alpha-enolase). The protective effect was epitope specific but also dependent on Fc-FCGR2B interaction on macrophages following the immune complex formation, resulting an increased IL-10 production and osteoclastogenesis reduction. The findings suggest that certain ACPAs could be protective in arthritis with therapeutic potentials.
2023-01-09 | PXD035180 | Pride
Project description:Anti-citrullinated protein antibodies (ACPAs) are one of the hallmarks in rheumatoid arthritis (RA), but the in vivo function remained unclear. To investigate the effects of ACPAs, we expressed monoclonal ACPAs derived from RA patients, and analyzed the functions in mouse models, as well as the reactivity to tissue and peptides/proteins. All ACPAs showed no arthritogenicity and could not induce pain-like behavior in mice whereas one of them (E4) profoundly protected against antibody-induced arthritis. E4 showed a tissue binding pattern restricted to skin epithelial cells, to macrophages and dendritic cells in lymphoid tissue and to cartilage from mouse and human arthritic joints. Proteomic analysis showed that E4 had a distinct binding pattern to macrophage and RA synovial fluid proteins (e.g. alpha-enolase). The protective effect was epitope specific but also dependent on Fc-FCGR2B interaction on macrophages following the immune complex formation, resulting an increased IL-10 production and osteoclastogenesis reduction. The findings suggest that certain ACPAs could be protective in arthritis with therapeutic potentials.
2023-01-09 | PXD035177 | Pride
Project description:The aim of this study was to compare gene expression between two pathological groups of human synovial fibroblasts (SF) from rheumatoid arthritis (RA) and osteoarthritis (OA) synovial tissues with normal SF from healthy individuals (HSF). We used microarray expression profiling in SF cultured from OA, RA and normal synovial tissues. We found larger numbers of transcripts with differential expression in OASF compared to the other groups than in RASF compared to HSF. This data demonstrate that cultured OASF display a more robust transcriptomic profile than RASF when compared to HSF. Synovial fibroblasts were obtained from 9 patients with rheumatoid arthritis (RASF), 11 sex and age matched adult healthy donors (HSF) and 11 sex and age matched patients with OA (OASF). SF were collected under similar subconfluent conditions 24h after serum addition. 31 microarray data were used for determine the statistical significance (p value) of the differences in gene expression.
2011-10-24 | E-GEOD-29746 | biostudies-arrayexpress
Project description:Splenocytes harvested from mice with FIA were cultured in vitro and stimulated with 0.01 mg/ml fibrinogen for 3 days. Enriched T cells were transferred into 6-week-old naïve SJL mice, which developed visible signs of arthritis within 2 weeks. Synovial array profiling of plasma from the arthritic recipient mice demonstrated autoreactive B cell responses against peptides representing native fibrinogen, and further spreading of the responses to target collagen type V, cartilage gp39, and citrullinated vimentin. Custom-spotted protein slides were with plasma samples from individual mice. Four slides were probed with plasma derived from naïve mice and five slides were probed with plasma derived from mice injected with FIA T cells.
2010-05-05 | E-GEOD-18025 | biostudies-arrayexpress
Project description:Background: Although the use of TNF inhibitors has fundamentally changed the way rheumatoid arthritis (RA) is treated, not all patients respond well. It is desirable to facilitate the identification of responding and non-responding patients prior to treatment, not only to avoid unnecessary treatment but also for financial reasons. In this work we have investigated the transcriptional profile of synovial tissue sampled from RA patients before anti-TNF treatment with the aim to identify biomarkers predictive of response. Methodology/Principal Findings: Synovial tissue samples were obtained by arthroscopy from 62 RA patients before the initiation of infliximab treatment. RNA was extracted and gene expression profiling was performed using an in-house spotted long oligonucleotide array covering 17972 unique genes. Tissue sections were also analyzed by immunohistochemistry to evaluate cell infiltrates. Response to infliximab treatment was assessed according to the EULAR response criteria. The presence of lymphocyte aggregates dominated the expression profiles and a significant overrepresentation of lymphocyte aggregates in good responding patients confounded the analyses. A statistical model was set up to control for the effect of aggregates, but no differences could be identified between responders and non-responders. Subsequently, the patients were split into lymphocyte aggregate positive- and negative patients. No statistically significant differences could be identified except for 38 transcripts associated with differences between good- and non-responders in aggregate positive patients. A profile was identified in these genes that indicated a higher level of metabolism in good responding patients, which indirectly can be connected to increased inflammation. Conclusions/Significance: It is pivotal to account for the presence of lymphoid aggregates when studying gene expression patterns in rheumatoid synovial tissue. In spite of our original hypothesis, the data do not support the notion that microarray analysis of synovial biopsy specimens can be used in the context of personalized medicine to identify non-responders to anti-TNF therapy before the initiation of treatment. All patients were hybridized in a dual channel reference design where the reference was always labeled with cy3 and the samples with cy5. In total, RNA was extracted from synovial biopsies of 62 patients. 18 patients were good responding, 30 moderate responding and 14 non-responding. Universal Human Reference RNA from Stratagene was used as reference. All samples were amplified with the RiboAmp II kit before labeling and hybridization.
2010-04-28 | E-GEOD-21537 | biostudies-arrayexpress